The overall aim of this project is to study the control of the expression of bovine leukemia virus (BLV) genome by a non-immunoglobulin protein that is found consistently in the plasma of BLV-infected cattle. This protein, referred to as the PBB factor, has been shown to block the transcription of the BLV genome in bovine lymphocytes. Specific aims of this project include: 1) Purification and Characterization of the PBB Factor. We have reported data showing that the PBB protein is neither an antibody nor an interferon molecule. Recently, we have made significant advancement towards the purification of the PBB factor. We propose to continue our efforts to purify the factory to homogeneity and to determine its biochemical and biophysical properties. 2) Elucidation of the Molecular Mechanisms of Action of the PBB Factor. The PBB factor has been shown to block the transcription of the BLV genome in short-term lymphocyte cultures. Using a nuclei-dependent cell-free RNA synthesizing system, we will determine whether the PBB factor per se or intracellular macromolecules induced by the PBB factor, are responsible for the transcriptional expression of the BLV genome.